Background: This study aimed to analyze the life expectancy and cause of death in osteoarthritis (OA) patients who underwent total knee arthroplasty (TKA) and to identify risk factors that affect long-term mortality rate after TKA. Methods: Among 601 patients, who underwent primary TKA due to OA by a single surgeon from July 2005 to December 2011, we identified patients who died after the operation using data obtained from the National Statistical Office of Korea. We calculated 5-, 10-, and 15-year survival rates of the patients and age-specific standardized mortality ratios (SMRs) compared to general population of South Korea according to the causes of death. We also identified risk factors for death. Results: The 5-year, 10-year, and 15-year survival rates were 94%, 84%, and 75%, respectively.The overall age-specific SMR of the TKA cohort was lower than that of the general population (0.69; P < 0.001). Cause-specific SMRs for circulatory diseases, neoplasms, and digestive diseases after TKA were significantly lower than those of the general population (0.65, 0.58, and 0.16, respectively; all P < 0.05). Male gender, older age, lower body mass index (BMI), anemia, and higher Charlson comorbidity index (CCI) were significant factors associated with higher mortality after TKA. Conclusion TKA is a worthwhile surgery that can improve life expectancy, especially from diseases of the circulatory system, neoplasms, and digestive system, in patients with OA compared to the general population. However, careful follow-up is needed for patients with male gender, older age, lower BMI, anemia, and higher CCI, as these factors may increase long-term mortality risk after TKA.

In addition to cellular damage, ischemia-reperfusion (IR) injury induces substantial damage to the mitochondria and endoplasmic reticulum. In this study, we sought to determine whether impaired mitochondrial function owing to IR could be restored by transplanting mitochondria into the heart under ex vivo IR states. Additionally, we aimed to provide preliminary results to inform therapeutic options for ischemic heart disease (IHD). Healthy mitochondria isolated from autologous gluteus maximus muscle were transplanted into the hearts of Sprague–Dawley rats damaged by IR using the Langendorff system, and the heart rate and oxygen consumption capacity of the mitochondria were measured to confirm whether heart function was restored. In addition, relative expression levels were measured to identify the genes related to IR injury. Mitochondrial oxygen consumption capacity was found to be lower in the IR group than in the group that underwent mitochondrial transplantation after IR injury (p < 0.05), and the control group showed a tendency toward increased oxygen consumption capacity compared with the IR group. Among the genes related to fatty acid metabolism, Cpt1b (p < 0.05) and Fads1 (p < 0.01) showed significant expression in the following order: IR group, IR + transplantation group, and control group. These results suggest that mitochondrial transplantation protects the heart from IR damage and may be feasible as a therapeutic option for IHD.

Background: Delta ceramic-on-ceramic (CoC) articulation affords excellent outcomes in primary total hip arthroplasty (THA). However, the safety and reliability of this bearing in revision THA need more evidence. This study aimed to report complications, radiological changes, clinical results, and survivorship of revision THA using Delta CoC articulation at minimum 5-year follow-up. Methods: We reviewed 118 revision THAs (113 patients: 68 men and 45 women) performed with use of Delta CoC bearing. Their mean age was 58.7 years (range, 30–90 years) and their mean body mass index was 24.6 kg/m 2 (range, 15.2–32.5 kg/m 2 ). These patients were followed up for 5–12 years (mean, 7.2 years). We evaluated squeak, grinding sensation, ceramic fracture, dislocation, periprosthetic joint infection (PJI), periprosthetic fracture, prosthetic loosening, ceramic wear, osteolysis, modified Harris hip score (mHHS), and survivorship with any reoperation after the revision as the endpoint. Results: Two patients (1.7%) had grinding sensation, but no patient had ceramic fracture. Reoperations were necessary in 9 hips (7.6%) due to PJIs in 2, stem loosening in 2, cup loosening in 2, recurrent dislocation in 2, and periprosthetic fracture in 1. No hip had measurable wear or osteolysis. The average mHHS improved from 53.3 points before the revision to 82.3 points at the final follow-up. Survivorship was 91.6% (95% confidence interval, 86.3%–96.9%) at 12 years. Conclusions The Delta ceramic bearing appeared a reliable option for revision THA, showing encouraging mid-term results with acceptable survivorship and a low complication rate.

Background: At the end of 2014, we implemented an online video to inform patients of the entire process from admission to rehabilitation after total hip arthroplasty (THA). In this study, we investigated the effectiveness of online video instruction in THA patients. Methods: Electronic medical records of 184 patients undergoing THA in 2014 (pre-video group) and 182 patients in 2015 (post-video group) were reviewed. We compared 1) the time to start wheelchair ambulation, 2) walker or crutch ambulation, 3) the length of hospital stay, 4) postoperative satisfaction using visual analogue scale (0–10 points), and 5) modified Harris Hip Score (mHHS) at postoperative 6 weeks. Results: In the post-video group, the time to start wheelchair ambulation (1.8 ± 0.6 vs. 2.4 ± 3.2 days, P = 0.021) and walker/crutch ambulation were faster (2.9 ± 1.2 vs. 3.8 ± 1.0 days, P = 0.016), and the hospital stay was shorter (8.2 ± 4.7 vs. 9.9 ± 7.8 days, P = 0.001) compared to the pre-video group. The visual analogue scale for satisfaction (7.84 ± 1.62 vs. 7.68 ± 1.85 points) and mHHS (89.59 ± 9.47 vs. 89.58 ± 8.59) were similar. Conclusion Online video instruction is an effective tool to expedite ambulation and reduce the hospital stay without compromising the clinical outcome and postoperative complications after THA.

Background: Conventional diagnostic approaches for adrenal tumors require multi-step processes, including imaging studies and dynamic hormone tests. Therefore, this study aimed to discriminate adrenal tumors from a single blood sample based on the combination of liquid chromatography-mass spectrometry (LC-MS) and machine learning algorithms in serum profiling of adrenal steroids. Methods: The LC-MS-based steroid profiling was applied to serum samples obtained from patients with nonfunctioning adenoma (NFA, n=73), Cushing’s syndrome (CS, n=30), and primary aldosteronism (PA, n=40) in a prospective multicenter study of adrenal disease. The decision tree (DT), random forest (RF), and extreme gradient boost (XGBoost) were performed to categorize the subtypes of adrenal tumors. Results: The CS group showed higher serum levels of 11-deoxycortisol than the NFA group, and increased levels of tetrahydrocortisone (THE), 20α-dihydrocortisol, and 6β-hydroxycortisol were found in the PA group. However, the CS group showed lower levels of dehydroepiandrosterone (DHEA) and its sulfate derivative (DHEA-S) than both the NFA and PA groups. Patients with PA expressed higher serum 18-hydroxycortisol and DHEA but lower THE than NFA patients. The balanced accuracies of DT, RF, and XGBoost for classifying each type were 78%, 96%, and 97%, respectively. In receiver operating characteristics (ROC) analysis for CS, XGBoost, and RF showed a significantly greater diagnostic power than the DT. However, in ROC analysis for PA, only RF exhibited better diagnostic performance than DT. Conclusion The combination of LC-MS-based steroid profiling with machine learning algorithms could be a promising one-step diagnostic approach for the classification of adrenal tumor subtypes.

Cancer immunotherapy, in the form of vaccination, adoptive cellular transfer, or immune checkpoint inhibitors, has emerged as a promising practice within the field of oncology. However, despite the developing field's potential to revolutionize cancer treatment, the presence of immunotherapeutic-resistant tumor cells in many patients present a challenge and limitation to these immunotherapies. These cells not only indicate immunotherapeutic resistance, but also show multi-modal resistance to conventional therapies, abnormal metabolism, stemness, and metastasis. How can immunotherapeutic-resistant tumor cells render multi-malignant phenotypes? We reasoned that the immune-refractory phenotype could be associated with multi-malignant phenotypes and that these phenotypes are linked together by a factor that acts as the master regulator. In this review, we discussed the role of the embryonic transcription factor NANOG as a crucial master regulator we named “common factor” in multi-malignant phenotypes and presented strategies to overcome multi-malignancy in immunotherapeutic-resistant cancer by restraining the NANOG-mediated multi-malignant signaling axis. Strategies that blunt the NANOG axis could improve the clinical management of therapy-refractory cancer.
Humans ; Immunotherapy ; Metabolism ; Neoplasm Metastasis ; Phenotype ; Transcription Factors ; Vaccination

Cancer immunotherapy, in the form of vaccination, adoptive cellular transfer, or immune checkpoint inhibitors, has emerged as a promising practice within the field of oncology. However, despite the developing field's potential to revolutionize cancer treatment, the presence of immunotherapeutic-resistant tumor cells in many patients present a challenge and limitation to these immunotherapies. These cells not only indicate immunotherapeutic resistance, but also show multi-modal resistance to conventional therapies, abnormal metabolism, stemness, and metastasis. How can immunotherapeutic-resistant tumor cells render multi-malignant phenotypes? We reasoned that the immune-refractory phenotype could be associated with multi-malignant phenotypes and that these phenotypes are linked together by a factor that acts as the master regulator. In this review, we discussed the role of the embryonic transcription factor NANOG as a crucial master regulator we named “common factor” in multi-malignant phenotypes and presented strategies to overcome multi-malignancy in immunotherapeutic-resistant cancer by restraining the NANOG-mediated multi-malignant signaling axis. Strategies that blunt the NANOG axis could improve the clinical management of therapy-refractory cancer.

The protein encoded by the Gene Associated with Retinoid-Interferon-Induced Mortality-19 (GRIM-19) is located in the mitochondrial inner membrane and is homologous to the NADH dehydrogenase 1-alpha subcomplex subunit 13 of the electron transport chain.Multiple sclerosis (MS) is a demyelinating disease that damages the brain and spinal cord.Although both the cause and mechanism of MS progression remain unclear, it is accepted that an immune disorder is involved. We explored whether GRIM-19 ameliorated MS by increasing the levels of inflammatory cytokines and immune cells; we used a mouse model of experimental autoimmune encephalomyelitis (EAE) to this end. Six-to-eight-week-old male C57BL/6, IFNγ-knockout (KO), and GRIM-19 transgenic mice were used; EAE was induced in all strains. A GRIM-19 overexpression vector (GRIM19 OVN) was electrophoretically injected intravenously. The levels of Th1 and Th17 cells were measured via flow cytometry, immunofluorescence, and immunohistochemical analysis. IL-17A and IFNγ expression levels were assessed via ELISA and quantitative PCR. IL-17A expression decreased and IFNγ expression increased in EAE mice that received injections of the GRIM19 OVN. GRIM-19 transgenic mice expressed more IFNγ than did wild-type mice; this inhibited EAE development. However, the effect of GRIM-19 overexpression on the EAE of IFNγ-KO mice did not differ from that of the empty vector. GRIM-19 expression was therapeutic for EAE mice, elevating the IFNγ level. GRIM-19 regulated the Th17/Treg cell balance.

Background: Osteopenia patients have a risk of fracture and may develop osteoporosis.We investigated physicians’ management of osteopenia patients in South Korea. Methods: A survey was conducted using a questionnaire including 6 items: (1) do you think anti-osteoporosis medications are necessary in osteopenia patients?; (2) what is your preference to manage osteopenia patients, except for anti-osteoporosis medications?; (3) what is your indication for the anti-osteoporosis medication in osteopenia patients?; (4) what kind of anti-osteoporosis medication do you prefer to treat osteopenia patients?; (5) do you use bisphosphonates?; and (6) if not, what is the reason for not using?. Results: Among the 173 participants, 150 (86.7%) replied that anti-osteoporosis medications were necessary in osteopenia patients. Indications for the medication were (1) past medical history of pathologic fracture in 85 (49.1%); (2) T-score <-2.5 on dual energy X-ray absorptiometry in 73 (42.2%); (3) previous history of osteoporosis in 44 (25.4%);(4) risk of fracture according to fracture risk assessment tool in 34 (19.7%); and (5) progressive bone loss in 31 (17.9%). One hundred and sixteen (67.1%) favored bisphosphonates, 93 (53.8%) selective estrogen-receptor modulator, and 24 (13.9%) hormone replacement therapy. Thirty-one (17.9%) replied that they do not use bisphosphonates due to (1) restricted reimbursement by the health insurance in 24 (77.4%); and (2) bisphosphonate-related complications in 19 (61.3%). Conclusions Most respondents (86.7%) thought anti-osteoporosis medications were necessary in osteopenia patients, but 17.9% of the respondents did not use bisphosphonates. Restricted reimbursement by the national health insurance was the major obstacle against the use of bisphosphonates.